Digital Commons Network^™

Identification And Characterization Of De Novo Germline Tp53 Mutation Carriers In Families With Li-Fraumeni Syndrome, Carlos C. Vera Recio

Dissertations & Theses (Open Access)

Li-Fraumeni syndrome (LFS) is an inherited cancer syndrome caused by a deleterious mutation in TP53. An estimated 48% of LFS patients present due to a de novo mutation (DNM) in TP53. The knowledge of DNM status, DNM or familial mutation (FM), of an LFS patient requires genetic testing of both parents which is often inaccessible, making de novo LFS patients difficult to study. Famdenovo.TP53 is a Mendelian Risk prediction model used to predict DNM status of TP53 mutation carriers based on the cancer-family history and several input genetic parameters, including disease-gene penetrance. The good predictive performance of Famdenovo.TP53 was demonstrated …

Standardizing New Diagnostic Tests To Facilitate Rapid Responses To The Covid-19 Pandemic, Xiao Dong

Dissertations & Theses (Open Access)

In order to enhance the data interoperability, an expeditious and accurate standardization solution is highly desirable for naming rapidly emerging novel lab tests, and thus diminishes confusion in early responses to pandemic outbreaks. This is a preliminary study to explore the roles and implementation of medical informatics technology, especially natural language processing and ontology methods, in standardizing information about emerging lab tests during a pandemic, thereby facilitating rapid responses to the pandemic. The ultimate goal of this study is to develop an informatics framework for rapid standardization of lab testing names during a pandemic to better prepare for future public …

Associations Of Perceived Overall Health, Psychological Distress, Functional Impairment, And Alcohol Use Among Older Adults Of Sexual Minority Status And Heterosexual Peers, Carolyn Tran

Dissertations & Theses (Open Access)

Background: Lesbian, gay, and bisexual (LGB) adults, 50 and older, are likely to have experienced mistreatment and discrimination, contributing to poor physical and mental health and risky behaviors, such as alcohol misuse. Few studies have examined the relationships between perceived health, psychological distress, functional impairment, and alcohol use of older LGB adults and heterosexuals.

Specific Aims: The specific aims were: (1) to determine if perceived overall health status is associated with psychological distress and functional impairment in sexual minority older adults compared to heterosexual older adults, and (2) to determine if sexual minority status moderates the relationship between psychological distress …

Exploring Motivational Factors To Pursue Genetic Counseling And Testing In Adolescent And Young Adult Cancer Patients, Megan Morand

Dissertations & Theses (Open Access)

Adolescent and young adult (AYA) cancer patients face a unique set of challenges when navigating cancer treatment and survivorship. For many patient populations, motivational factors to pursue genetic counseling/testing have been described, but these motivational factors in AYA cancer patients have yet to be explored. The goal of this study was to describe AYA cancer patients’ decision-making process, including motivational factors and barriers as it relates to genetic counseling/testing. We conducted a qualitative study consisting of semi-structured interviews with 30 individuals from the AYA Program at MD Anderson Cancer Center who attended or were referred to a genetic counseling appointment. …

Investigating Diffusion Tensor Imaging Correlates Of Cognitive Impairment In Idiopathic Normal Pressure Hydrocephalus And Alzheimer's Disease, Omar Hasan, Omar Hasan

Dissertations & Theses (Open Access)

Modest expansion of the human brain cerebrospinal fluid (CSF)-filled ventricles is normal with aging, and because of this, it can be difficult for physicians to accurately diagnose and treat enlarged ventricles (ventriculomegaly), called hydrocephalus¹ (fluid or water in the brain) Ventriculomegaly occurs due to an obstruction (such as a blood clot or tumor), or a change in CSF absorption². Primary hydrocephalus, also called idiopathic normal pressure hydrocephalus (iNPH), is non-obstructive and may be comorbid with other neurodegenerative diseases such as Alzheimer’s disease (AD) or frontotemporal dementia (FTD). Clinically, it can be difficult to tell whether the pathophysiological …

Mixture Model Approaches To Integrative Analysis Of Multi-Omics Data And Spatially Correlated Genomic Data, Ziqiao Wang

Dissertations & Theses (Open Access)

Integrative genomic data analysis is a powerful tool to study the complex biological processes behind a disease. Statistical methods can model the interrelationships of the involved gene activities through jointly analyzing multiple types of genomic data from different platforms (vertical integration), or improve the power of a study through aggregating the same type of genomic data across studies (horizontal integration). In this dissertation, we propose statistical methods and strategies for integrative multi-omics data in association analysis of disease phenotypes, with an emphasis on cancer applications.

We develop a new strategy based on horizontal integration by leveraging publicly available datasets into …

Disability Awareness Education And Implications For Genetic Counselor Training, Lauren Douglas, Chelsea Wagner, Jennifer Czerwinski, Myla Ashfaq, Rebecca Lunstroth, Rose Vukoic

Dissertations & Theses (Open Access)

The genetic counseling (GC) community has faced criticism concerning the duality of promoting patient autonomy while advocating for individuals with disabilities. Research suggests that focusing on the education of GC students could ensure GCs feel prepared to have conversations about disability, as well as strengthen the relationship with the disability community. This study aimed to evaluate the landscape of GC disability awareness education to identify gaps and strengths. The study also aimed to assess attitudes and perspectives of GCs and the disability community to identify content that should be included in GC student’s disability awareness curriculum. GCs and members of …

Role Of Methyltransferase Like-3 (Mettl3) In Pancreatic Ductal Adenocarcinoma (Pdac) Progression, Bhargavi Brahmendra Barathi

Dissertations & Theses (Open Access)

Pancreatic Ductal Adenocarcinoma (PDAC) is an aggressive cancer with about a 10% five-year survival rate. The grim prognostic situation of pancreatic cancer patients underlines the need to identify novel molecular targets. Recent studies have brought to attention, the need to therapeutically exploit epigenetic pathways, apart from only targeting genetic mutations to effectively combat PDAC. To that effect, METTL3-mediated post-transcriptional methylation of RNA transcripts have been shown to contribute to cancer progression in multiple cancer types.

METTL3 deposits methyl groups onto adenosine bases within specific consensus sequences in RNA, resulting in the formation of N-6 methyl adenosine (m6A). m6A is the …

Assessing Genetic Counselors' Clinical Approach And Practices Regarding Pathogenic/Likely Pathogenic Variant Downgrades, Grant Bonesteele

Dissertations & Theses (Open Access)

Although rare, variant downgrades from a pathogenic/likely pathogenic (P/LP) variant to a variant of uncertain significance can have a significant impact on patients and their families in the clinical cancer setting. However, there is a lack of literature about how to approach these potentially challenging cases as a genetic counselor. Therefore, we aimed to characterize genetic counselors’ experiences, approach, and practices to variant downgrade cases using an online survey. The survey asked participants how they would approach variant downgrade scenarios involving the CDH1 or ATM genes with variable family histories. Genetic counselors appear to be united in whether they would …

Evaluating Insurance Approval Rates Of Exome Sequencing And Its Effect On Minority Patients' Access To Genetic Care, Katlyn Frane

Dissertations & Theses (Open Access)

Exome sequencing (ES) is often a standard step in the genetic testing process for patients with rare or complex disease. Despite clinical implementation of ES, insurance companies (payers) continue to deny this test. We investigated if the payer barrier is influenced by payer type, and if other demographic or clinical information correlated to ES approval and obtainment. To do this, a retrospective chart and clinical database review was completed on patients seen at a tertiary care center and community-based clinic. Patient demographics, clinical indications, and testing recommendations and outcomes were used to assess ES approval and obtainment. We found that …

Investigating Barriers Experienced By Underrepresented Minorities In Becoming A Competitive Genetic Counseling Applicant, Katie Huang

Dissertations & Theses (Open Access)

Representation for both racial/ethnic and gender identity minorities in genetic counseling (GC) remains the lowest among similar healthcare professions. Barriers that underrepresented minority (URM) individuals face in becoming a competitive GC applicant have not yet been described. Academic capital (AC) is a theoretical framework describing the social processes necessary for individuals to navigate and succeed in higher education. This study aimed to characterize barriers experienced by applicants who self-identify as underrepresented and to explore how AC could identify areas for intervention. Prospective GC applicants for the 2021/2022 cycles were recruited to complete an anonymous online survey in Qualtrics through a …

Survival Analysis Of Colorectal Cancer Patients With Liver Metastasis, Brandon O’Grady

Dissertations & Theses (Open Access)

Background- Colorectal cancer is the third most common cancer in the world. I investigated the survival rates among colorectal cancer patients diagnosed with hepatic metastasis to see if any variables are associated colorectal risk and survival. Methods- Patients were diagnosed from 2000-2019 and collected through MD Anderson’s database. A descriptive analysis, univariate analysis, Kaplan-Meier with Mantel log-rank test, Cox proportion hazard regression and a Stratified Cox Model was performed to investigate death. A competing risk regression was implemented to investigate liver recurrence. Results- There was a clear difference in the survival outcome between liver surgery patients and non-liver surgery patients …

The Comparative Effect Of Automated Reminders/Recalls Interventions On The Appointments Rate Of Adolescent Wellness Care Visit, Biai Dominique Elmir Digbeu

Dissertations & Theses (Open Access)

An Adolescent Wellness Care (AWC) visit is an annual preventive doctor visit predestined to assess the overall health of adolescents aged between 12 and 21 years old. Compared to their younger counterparts, adolescents who are using public insurance are at risk of not completing AWC visits due to several factors related to age or providers disparities in their living environment. This research was a quasiexperimental study aiming to compare two methods of automated Reminders/Recalls (RR) interventions, ‘phone-only’ versus ‘phone-and-text’, in order to evaluate which method is more effective in helping parents/guardians or young adults to schedule an AWC visit. A …

Characterization Of Age-Associated Copd Progression In The Copd Gene Cohort, Lauryn A. Winter

Dissertations & Theses (Open Access)

Chronic obstructive pulmonary disease (COPD) is a progressive and debilitating lung disease affecting primarily older adults. Incidence, morbidity and mortality from COPD are increasing worldwide. The purpose of this study was to determine the associations between age at baseline and markers of disease progression in COPD patients using data generated by the Genetic Epidemiology of COPD (COPD Gene) study. Participants with COPD were stratified by age (younger: age <65 years, elderly: age ≥ 65 years) and disease characteristics (lung function, exercise tolerance, exacerbation history, and comorbidity burden) at baseline and five-year follow up were compared between groups. Associations between age group and changes in these measures were also assessed. Disease characteristics differed significantly between elderly and younger COPD patients at both study visits. Elderly COPD patients had worse lung function and more comorbidities than younger COPD patients, while younger COPD patients reported more dyspnea and more frequent and severe exacerbations than elderly COPD patients. Following covariate adjustment, elderly participants were less likely than younger participants to develop new frequent exacerbations over the study period (relative risk ratio (95% confidence interval): 0.42 (0.20, 0.87)). There were no other significant associations between age group and markers of disease progression. These results suggest that although elderly COPD patients exhibit evidence of more severe lung function impairment than younger COPD patients, the rate of disease progression is similar between elderly and younger patients. However, further exploration is needed to understand the possible contribution of survivorship bias to this finding. Nevertheless, this study supports the importance of early detection and early intervention to slow disease progression and maximize both life expectancy and quality of life for COPD patients.

P53 Drives A Transcriptional Program That Elicits A Non-Cell-Autonomous Response And Alters Cell State In Vivo, Sydney Moyer

Dissertations & Theses (Open Access)

Cell stress and DNA damage activate the tumor suppressor p53, triggering transcriptional activation of a myriad of target genes. The molecular, morphological, and physiological consequences of this activation remain poorly understood in vivo. We activated a p53 transcriptional program in mice by deletion of Mdm2, a gene which encodes the major p53 inhibitor. By overlaying tissue-specific RNA-sequencing data from pancreas, small intestine, ovary, kidney, and heart with existing p53 ChIP-sequencing, we identified a large repertoire of tissue-specific p53 genes and a common p53 transcriptional signature of seven genes which included Mdm2 but not p21. Global p53 activation …

Influence Of Genetic Counselor Personal Or Family Medical History On Genetic Counseling Specialization And Practice, Kaitlyn K. Amos Ms

Dissertations & Theses (Open Access)

A personal or family medical history inherently becomes part of a genetic counselor’s life story. Yet the degree to which a counselor’s experience influences his or her specialty choice and their psychosocial practice is unexplored. A medical diagnosis may foster a counselor’s capacity for greater empathy, understanding and rapport-building self-disclosure. Conversely, it could lead to interruptive countertransference, compassion fatigue, and eventually burnout. However, research has not specifically investigated this intersection. Therefore, the aim of this study was to explore the impact of a genetic counselor’s personal or family medical history on his or her choice of practice area, as well …

Asthma-Copd Overlap Syndrome And Disease Progression In The Copdgene Cohort Study, Caitlyn Winter

Dissertations & Theses (Open Access)

Chronic Obstructive Pulmonary Disease (COPD) is a debilitating and degenerative lung disease characterized by progressive airway obstruction and alveolar destruction. When asthma and COPD co-occur and interact, with asthma having been diagnosed first, the resulting respiratory disease is called Asthma-COPD Overlap Syndrome (ACOS). Current research suggests that persons with ACOS may have more severe respiratory disease and lifestyle limitations than those with either disease alone. The purpose of the current study was to determine if and how disease progression differs in patients with ACOS versus COPD only, using data collected during the COPDGene cohort study. Demographic characteristics and disease outcome …

Applications Of Statistical Methods Studying The Impact Of Mobilization Regimes On The Total Collection Yield Of Hematologic Stem Cell, Mengchen Ding

Dissertations & Theses (Open Access)

Hematologic malignancies are cancers that develop in the blood, bone marrow, and lymph nodes. Hematopoietic stem cell transplantation (HSCT) is a critical therapeutic approach that contributes to offer a potential cure for hematologic cancers and other hematologic disorders by replacing abnormal bone marrow with healthy bone marrow components to help bone marrow function recovery. Peripheral blood is the primary resource for collecting hematopoietic stem cells (HSCs). The collection yield of HSCs is critical for successful transplantation. Few articles have discussed this topic that the collection of stem cells not only from healthy donors but also from donors with a hematologic …

Sine Oculis Homeobox Homolog 1 (Six1) Plays A Critical Role In The Progression Of Pulmonary Fibrosis., Cory Wilson

Dissertations & Theses (Open Access)

Idiopathic pulmonary fibrosis (IPF) is the most common idiopathic interstitial pneumonia with a median survival time of 2-4 years after diagnosis. The alarming mortality rate is due to the lack of effective treatments. IPF is a chronic disease that is characterized by alveolar destruction due to increasing extracellular matrix deposition that leads to poor lung compliance, impaired gas exchange, and ultimately respiratory failure. Repetitive alveolar epithelial injury is a central process to the underlying pathology with injury to the type II alveolar epithelial cells (AT2) specifically being a key player in the pathogenesis of IPF. Recent studies have shown that …

Costs Of Coronary Artery Bypass Grafting And Percutaneous Coronary Intervention In Texas, Saleh Hamed Alsarhan

Dissertations & Theses (Open Access)

Background: Coronary artery bypass grafting (CABG) surgery and percutaneous coronary intervention (PCI) procedures have been associated with substantial financial costs in Texas. The annual hospital charges in 2016 for CABG surgeries and PCI procedures in Texas were $3.6 billion and $4.1 billion, respectively. Recently, these two procedures have become a target for bundled payment initiatives. Due to the lack of information about the demographics and variations associated with CABG and PCI episode payments for commercially insured patients, more research needs to be conducted to understand the magnitude of payments and the drivers of variation in payments in Texas. Objective: This …

Heat Stress Related Symptoms And Pulmonary Function In Oil Spill Response And Cleanup Workers Following The Deepwater Horizon Disaster, Yiyao Li

Dissertations & Theses (Open Access)

Objective: The objective of this study was to estimate the relationship between heat stress and pulmonary function among OSRC workers following the Deepwater Horizon (DWH) disaster. Methods: Pulmonary function test results were analyzed from a cohort of oil spill response and cleanup workers 1-3 years following the DWH disaster (N=5,131). Proxies for heat stress was employed by using information on heat stress-related symptoms as well as a questionnaire on stopping work due to heat reported during a structured telephone enrollment questionnaire. Associations between heat stress proxies and lung function were estimated using multivariable linear models and binomial logistic regression models …

Area-Level Landfill Density And Asthma Prevalence In Urban Texas Areas, Jessica Meighan Herrin

Dissertations & Theses (Open Access)

Environmental exposures, especially air pollutants, pose a threat for an increase in asthma prevalence. In particular, hydrogen sulfide (H2S) gas can cause severe health effects closely resembling asthmatic symptoms. Ambient concentrations of H2S gas correlates with the amount of solid waste found in landfills. The potential for adverse health risks associated with H2S emitted from landfills is of concern for those populations living in close proximity to landfills. Asthma is one of the adverse health effects that can occur due to H2S exposure. However, there is a lack of detailed studies characterizing possible associations between the density of landfills and …

Cross-Sectional Analysis Of The Relationship Between Violent Crime And Mental Health Disorders In A Sample Of Homeless Adults Recently Released From Jail, Addison Ransom

Dissertations & Theses (Open Access)

Adverse mental health conditions among incarcerated populations are high, and treatment for these conditions is particularly low. Additionally, there is a culture of stigma in the United States towards those with mental health conditions and violent criminal history, contributing to mass incarceration. The present cross-sectional study sought to assess the association between violent criminal history and mental health symptoms among recently incarcerated homeless adults in Dallas, Texas. This study included 230 participants, taking place at The Bridge Homeless Recovery Center, evaluating non-violent versus violent criminal history. Outcome measures of positive screens for post-traumatic stress disorder, generalized anxiety disorder, and depression …

Effect Of The Expanded Prospective Payment System On Dialysis Initiation, The Usage Of Erythropoiesis-Stimulating Agents, And Medicare Expenditures, Lu Zhang

Dissertations & Theses (Open Access)

In January 2011, the U.S. Centers for Medicare & Medicaid Services (CMS) implemented the expanded prospective payment system (PPS) for financing the management of end-stage renal disease (ESRD). Expanded PPS may not only change healthcare providers’ decisions about patient care by removing the financial incentives associated with the previous composite rate payment methodology, but also change the Medicare expenditures associated with various treatment patterns by using a constant base rate for all dialysis modalities. This study aimed to examine the effect of the expanded PPS on providers’ decisions on timing of dialysis initiation and ESA utilizations in ESRD patients as …

Hospital Market Analysis Using A Cohort Of Privately Insured Patients With Total Hip And Knee Replacement Procedures, Elifnur Yay Donderici

Dissertations & Theses (Open Access)

Background: Several recent studies have analyzed the contribution of hospital inpatient prices and utilization to variation in medical spending. However, it is still unknown how the drivers of spending for specific procedures differ within privately insured patients. Next, the market concentration of hospitals has been a matter of concern for several decades. However, researchers usually calculate Herfindahl-Hirschman index (HHI) as a measure of market concentration or power, but there is a drawback of using this measure. Hospitals sell differentiated products, and the HHI measure does not take this differentiation into account in its formulation (Gaynor and Town, 2011). Objective: First …

Health Disparities Across Funcitonal Disability Groups, Katherine Sanches

Dissertations & Theses (Open Access)

Background: People with disabilities experience higher rates of chronic disease and poor health status compared to those without disability. People with disabilities do not participate in community health programs to the same degree as those without disability due to social, programmatic, and environmental barriers. The Community Health Inclusion Index (CHII) is a community health assessment tool which evaluates the degree to which community-level health promoting opportunities to promote nutrition and physical activity are inclusive and accessible to people with disabilities. The CHII assess barriers to inclusion across five domains: build environment, equipment, program/services, staff, and policies. Objective: The purpose of …

The Direct Primary Care Model: Practice Characteristics And Patient Experience, James David Miller

Dissertations & Theses (Open Access)

The Direct Primary Care practice model has been growing in both number of practices and public awareness. However, there has been little academic research about this emerging practice model. This research is aimed to describe the current state of the DPC practice model by examining the services provided, geographic distribution of practices, statistical distribution of membership fees, demographic characteristics of physicians using the model and to determine whether regional pricing variation existed. In addition, differences were analyzed between the patient satisfaction levels in DPC and fee-for-service practices. A dataset was created by visiting the website of all known, non-corporate, DPC …

Determining The Racial And Ethnic Differences In Neonatal Intensive Care Unit Admission Rates, Youngran Kim

Dissertations & Theses (Open Access)

Background: Recent trends show that the utilization of neonatal intensive care unit (NICU) has extended beyond severely ill infants and increased substantially across all birth weights. However, little is known about what drives the growth of NICU admission rates and whether these trends differ by race/ethnicity. Methods: The study used 2008-2018 Natality Files with restricted use of state and county-level information. Crude and risk-adjusted NICU admission rates, overall and stratified by birth weight group, were compared between black and white infants and between Hispanic and white infants. Kitagawa decomposition and Oaxaca-Blinder decomposition analyses were conducted for the temporal increase in …

The Impact Of Bullying Victimization And Sexual Orientation On The Severity Of Suicidal Behavior, Annalyn Demello

Dissertations & Theses (Open Access)

Background: Lesbian, gay, and bisexual (LGB) youth face a disproportionate risk of suicidal ideation and attempt compared to their heterosexual counterparts. The Minority Stress Theory and Interpersonal Theory of Suicide posit that chronic stress, which can occur as a result of bullying victimization, can lead to loneliness, self-hate, and suicidal ideation. The escalation from ideation to attempt can occur quickly, and most youth who survive suicide attempts pursue subsequent, riskier attempts. It is crucial to intervene when behaviors are less severe. The primary aim of this study was to compare the magnitudes of association between independent variables (bullying and sexual …

Development And Preliminary Psychometric Testing Of The Drake Atrial Electrogram Assessment Survey: Daegas©, Jeanette Drake

Dissertations & Theses (Open Access)

Background: Critical care nurses (CCNs) who care for postoperative cardiac surgery patients need specialty knowledge, for example, knowledge of atrial electrograms (AEGs). An inadequate audit trail exists for psychometric performance of instruments to measure CCN knowledge of AEGs. A 29-item survey previously pilot tested with a convenience sample of CCNs in the Pacific Northwest had a Kuder-Richardson-20 estimate of internal consistency of .75. The survey was revised to 20 items (14 knowledge and 6 AEG interpretation) and named the Drake Atrial Electrogram Assessment Survey (DAEGAS).

Objectives: The study objectives were to assess evidence for content validity (content validity …